The present invention relates to plasmid constructs encoding and expressing porcine circovirus (PCV for Porcine CircoVirus) immunogens responsible for the PMWS syndrome (Porcine Multisystemic Wasting Syndrome or Post-Weaning Multisystemic Wasting Syndrome), to methods of vaccination and to DNA vaccines, as well as to methods of producing and of formulating these vaccines. All documents cited herein, and all documents cited in documents cited herein are hereby incorporated herein by reference.
PCV was originally detected as a noncytopathogenic contaminant in pig kidney cell lines PK/15. This virus was classified among the Circoviridae with the chicken anaemia virus (CAV for Chicken Anaemia Virus) and the PBFDV virus (Pscittacine Beak and Feather Disease Virus). These are small nonenveloped viruses (from 15 to 24 nm) whose common characteristic is to contain a genome in the form of a circular single-stranded DNA of 1.76 to 2.31 kilobases (kb). It was first thought that this genome encoded a polypeptide of about 30 kDa (Todd et al., Arch. Virol., 1991, 117: 129-135). Recent work has however shown a more complex transcription (Meehan B. M. et-al., J. Gen. Virol., 1997, 78: 221-227). Moreover, no significant homologies in nucleotide sequence or in common antigenic determinants are known between the three species of circoviruses known.
The PCV derived from PK/15 cells is considered not to be pathogenic. Its sequence is known from B. M. Meehan et al., J. Gen. Virol. 1997 (78) 221-227. It is only very recently that some authors have thought that strains of PCV could be pathogenic and associated with the PMWS syndrome (G. P. S. Nayar et al., Can. Vet. J., 1997, 38: 385-387 and Clark E. G., Proc. Am. Assoc. Swine Prac. 1997: 499-501). Nayar et al. have detected PCV DNA in pigs having the PMWS syndrome using PCR techniques.
Monoclonal and polyclonal antibodies directed against circoviruses found in pigs having the symptoms of the PMWS syndrome have been able to demonstrate differences between these circoviruses and the porcine circoviruses isolated from culture of PK-15 cells (Allan G. M. et al. Vet Microbiol., 1999, 66: 115-123).
The PMWS syndrome detected in Canada, the United States and France is clinically characterized by a gradual loss of weight and by manifestations such as tachypnea, dyspnea and jaundice. From the pathological point of view, it is manifested by lymphocytic or granulomatous infiltrations, lymphadenopathies and, more rarely, by hepatitis and lymphocytic or granulomatous nephritis (Clark E. G., Proc. Am. Assoc. Swine Prac. 1997: 499-501; La Semaine Vétérinaire No. 26, supplement to La Semaine Vétérinaire 1996 (834); La Semaine Vétérinaire 1997 (857): 54; G. P. S. Nayer et al., Can. Vet. J., 1997, 38: 385-387).
These circoviruses obtained from North America and from Europe are very closely related, with a degree of identity of more than 96% of their nucleotide sequence, whereas the degree of identity is less than 80% when the nucleotide sequences of these circoviruses are compared with those of porcine circoviruses isolated from PK-15 cells. Accordingly, two viral subgroups have been proposed, PCV-2 for the circoviruses associated with the PMWS syndrome and PCV-1 for the circoviruses isolated from the PK-15 cells (Meehan B. M. et al., J. Gen. Virol., 1998, 79: 2171-2179. WQ-A-9918214).